The photooxidation of artemisinic (arteannuic) acid (Compound 1), has been studied by several groups in a search for a route from this relatively abundant constituent of the plant Artemisia annua to the antimalarial drug artemisinin (qinghaosu) (Compound 3) which is present in the same plant in very low concentration.
Because there is far more artemisinic acid (Compound 1) than artemisinin (Compound 3) in Artemisia annua, the conversion of the former to the latter has received a great deal of attention. Prior synthetic conversion of 1 to 3 required a greater number of steps, produced a yield of approximately 7% and required the use of column chromatography for purification of the resulting artemisinin. Other attempts to simplify the process resulted in conversion of artemisinic acid into desoxyartemisinin, but did not . result in conversion to artemisinin.
The novel process described herein provides increased yields of artemisinin by photooxidation of dihydroartemisinic acid (Compound 2) in a simple procedure which does not require column chromatography. Because artemisinic acid can be easily isolated from Artemisia annua and purified without recourse to column chromatography, the process disclosed herein provides a simpler, less costly, and more efficient process for producing artemisinin. Furthermore, the novel process can more than double production of artemisinin from the plant material by utilization of artemisinic acid, which was previously discarded.
Another advantage of this process is that it provides a short route for deuterium-labelled artemisinin.